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Alert! “Cats Can Literally Make You Crazy.” Wait! “Cats Don’t Cause Mental Illness.” The news headlines are as alarming as they are contradictory. All refer to Toxoplasma gondii, a brain parasite carried by our feline companions that infects roughly one in three people.
Scientists have long hypothesized that T. gondii plays a role in mental illness, including schizophrenia. But though more than 100 studies have found a correlation, none has shown that the parasite actually causes mental illness. So what’s really going on? Here’s what you need to know:
How do humans get infected?
T. gondii is not a bacterium or a virus, but a single-celled microscopic organism distantly related to the parasite that causes malaria. Cats get T. gondii and the disease it causes, toxoplasmosis, by eating infected rodents, birds, and other animals. Estimates suggest about 40% of cats in the United States are infected; most don’t show any symptoms, but they can develop jaundice or blindness and experience personality changes if the parasite spreads to the liver or nervous system.
In the first few weeks after infection, a cat can shed millions of hardy egg pods called oocysts into its litter box each day. Although some people get toxoplasmosis from direct contact with domestic cats and cat feces, many more are infected when oocysts shed by cats make it into the soil and water, where they can survive for a year or longer.
Only about 11% of people are infected with T. gondii in the United States, though rates are much higher in regions where people eat more raw meat or sanitation is poor; for example, infection rates exceed 90% in some parts of Europe and South America. In healthy people, toxoplasmosis often causes a flulike illness or no symptoms at all. But it can occasionally be dangerous—or even fatal—in those with weakened immune systems. Antibiotics can treat the infection, though drugs may not completely banish the parasite.
The single-celled parasite Toxoplasma gondii in the process of dividing.
Ke Hu and John M. Murray/Wikimedia CommonsCC-BY 4.0
Why do scientists think toxoplasmosis could cause mental illness?
Most of the evidence comes from rodents, which develop bizarre behaviors when infected with T. gondii. They lose their fear of the smell of cat urine, in some cases walking right into the jaws of waiting felines. Scientists think T. gondii alters brain function by forming cysts in regions that process fear and decision-making. The cysts may also affect behavior by ramping up levels of dopamine, a neurotransmitter involved in reward and risk-taking. There’s some evidence that T. gondii can rewire the brain permanently, making mice unafraid of cats even long after the parasite has been cleared.
T. gondii also forms cysts inside human neurons. In people with HIV or other immune-weakening conditions, the cysts can grow and replicate, causing deadly brain inflammation, dementia, and psychosis. Although scientists have long assumed the cysts are benign in healthy people, a growing body of data suggests T. gondii infection can alter personality and increase the chance of developing schizophrenia and other mental illness. Even without directly infecting the brain, a chronic T. gondii infection can ramp up inflammation, and inflammation has been linked to mental disorders such as schizophrenia, autism, and Alzheimer’s disease.
How strong is the evidence that this happens in people?
Here’s where things get tricky. Although the mechanistic hypothesis for how toxoplasmosis could cause mental illness is “very compelling,” it’s extremely difficult to test in a human population, says Karen Sugden, a geneticist at Duke University in Durham, North Carolina.
In a 2016 study, Sugden found that 200 New Zealanders infected with T. gondii didn’t have significantly higher odds of schizophrenia or any other mental disorder. But she says the study doesn’t prove that the parasite has no link to mental illness. Schizophrenia usually doesn’t emerge until the late teens or 20s.
To find out if toxoplasmosis causes schizophrenia, Sugden says one would have to know if participants were exposed to T. gondii as children or teens—before they developed a mental illness. But her study only tested for the parasite at age 38, too late to tell whether the infection or schizophrenia came first. Many correlational studies—including Sugden’s—don’t have access to that kind of information, she notes.
Sugden’s study, like others, also relied on small sample sizes. Schizophrenia is a rare disease, typically occurring in about 1% of the population. To achieve robust statistical results, researchers need to follow tens or even hundreds of thousands of people over long periods, testing for T. gondii and mental illness periodically to determine which came first, she says.
Have any studies addressed the timing of T. gondii and the onset of mental illness?
Last month, scientists published the first study to address timing in more than 80,000 Danish blood donors. Yet even in this large group, the number of schizophrenia diagnoses was fairly small: 151 people. The study found that people who were exposed to T. gondii had 47% increased odds of being diagnosed with schizophrenia. When the researchers looked at the timing issue—narrowing their analysis to 28 people who were first diagnosed with schizophrenia after testing positive for T. gondii exposure—they found that these individuals were 2.5 times more likely to develop the disease post-exposure.
That number lines up with other large, correlational studies, which have also found a roughly 2.5-fold increase in the odds of schizophrenia diagnosis in infected people, says Robert Yolken, a virologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland, and one of the authors of the Danish study. Because the overall rate of schizophrenia diagnosis is rare, however, infection only slightly increases the odds—from say, a one in 100 chance to a two to three in 100 chance of a schizophrenia diagnosis.
Yolken and other researchers suspect that T. gondii may not cause mental illness by itself, but interacts with genetic variants that make some people more susceptible. This adds T. gondii to the list of environmental factors that increase schizophrenia risk by a small but measurable amount, such as prenatal infection and socioeconomic status, he says.
So should you worry?
Even if you do become one of the roughly one in three people who carry a latent T. gondii infection, current research suggests the odds of developing schizophrenia as a direct result of toxoplasmosis infection are low.
How low? It would be premature to put a number on it, but it appears to be on par with other schizophrenia risk factors you probably don’t worry about, such as living in a city.
“The advice for avoiding toxoplasmosis infection has already been around for a really long time,” Sugden says. It includes keeping cats indoors where they can’t hunt infected animals, disposing of cat litter daily, properly cooking food, and other recommendations from the U.S. Centers for Disease Control and Prevention.
Yolken, who has two cats, doesn’t want people to be overly worried about their pets—just worried enough to support research for a toxoplasmosis vaccine for cats and better treatments for both cats and people. He thinks it will only be possible to truly pin down T. gondii’s effects on mental health once it’s possible to prevent and treat the parasite. The need is most urgent in countries where infection rates are high, he notes. “The question is, how much better could people be doing if we could get rid of toxoplasmosis?” he says. “The risk may be low, but we could lower it more.”